This Reuters Health article was published Friday in Scientific American (www.sciam.com). It's about some recently published research out of the UK. "The report describes 66 patients who were followed for at least one year after an initial diagnosis of 'possible or definite parkinsonian syndrome'. After follow-up of around 29 months, the clinical diagnosis had changed in 22 patients (33 percent). Most of the changes (82 percent) occurred in the first year. Reason for the modified diagnoses included development of additional clinical features, early thinking impairment, x-ray results, poor response to drug therapy, and lack of disease progression. More than a third of those who were misdiagnosed with Parkinson's disease were eventually determined to have a related problem called dementia with Lewy bodies."

"The major implication is that doctors making the diagnosis of a parkinsonian syndrome need to be aware of the potential inaccuracy of the initial diagnosis and be prepared to review patients regularly (probably at least yearly) and change it as appropriate," Counsell said in an interview with Reuters Health. "A change in diagnosis may also require a change in treatment, either stopping unnecessary treatment or starting new treatment."

The medical journal abstract indicates that PD is over-diagnosed, according to this research.

Here's a copy of the Reuters Health article and the related medical journal abstract. (I read the article on the LBDcaregivers Yahoo!Group.)

November 14, 2008
Diagnosis of parkinsonian syndrome often changes
By Michelle Rizzo

NEW YORK (Reuters Health) - The cause of a parkinsonian syndrome is not always clear when the symptoms first appear, and the diagnosis often changes over time, according to a paper in the Journal of Neurology, Neurosurgery, and Psychiatry. Use of rigid criteria does not necessarily help make the diagnosis.

Parkinsonian syndrome refers to conditions that have the symptoms of Parkinson's disease, such as tremors, stooped posture, slowness, and shuffling gait. The term is simply used to describe a patient's symptoms; Parkinson's disease may or may not be the actual cause. For instance multiple small strokes can cause a parkinsonian syndrome.

"Accurate diagnosis of Parkinson's disease is important both in clinical practice, where it will influence management, and in research, where the validity of findings may be compromised if studies include (different) conditions," Dr. Carl Counsell, of the University of Aberdeen, UK, and colleagues write.

The report describes 66 patients who were followed for at least one year after an initial diagnosis of "possible or definite parkinsonian syndrome."

After follow-up of around 29 months, the clinical diagnosis had changed in 22 patients (33 percent). Most of the changes (82 percent) occurred in the first year. Reason for the modified diagnoses included development of additional clinical features, early thinking impairment, x-ray results, poor response to drug therapy, and lack of disease progression.

More than a third of those who were misdiagnosed with Parkinson's disease were eventually determined to have a related problem called dementia with Lewy bodies.

As part of their study, the researchers applied research criteria using records from patients' initial evaluation and latest yearly follow-up. In 8 patients (12 percent), the latest clinical diagnosis differed from the research-based diagnosis.

"The major implication is that doctors making the diagnosis of a parkinsonian syndrome need to be aware of the potential inaccuracy of the initial diagnosis and be prepared to review patients regularly (probably at least yearly) and change it as appropriate," Counsell said in an interview with Reuters Health. "A change in diagnosis may also require a change in treatment, either stopping unnecessary treatment or starting new treatment."

SOURCE: Journal of Neurology, Neurosurgery, and Psychiatry, November 2008.

BACKGROUND: Accurate diagnosis of the cause of parkinsonism during life can be difficult, particularly at presentation, but few studies have described changes in clinical diagnosis over time and the effect of applying strict research criteria.

METHODS: Incident patients with a possible/probable diagnosis of degenerative or vascular parkinsonism had a standardised assessment at diagnosis and at yearly intervals thereafter at which the most likely clinical diagnosis was recorded without strict application of research criteria. Four years after the beginning of the incident period, formal research criteria were applied retrospectively using patient records at baseline and the latest yearly follow-up.

RESULTS: Of 82 incident patients, 66 underwent at least 1 year of follow-up. After a median follow-up of 29 months, clinical diagnosis had changed in 22 (33%). Most (82%) changes occurred in the first year and were due to the development of atypical clinical features, particularly early cognitive impairment; the results of brain imaging; responsiveness to levodopa; and the rate of disease progression. Diagnosis on research criteria differed from latest clinical diagnosis in eight participants (12%). Research criteria gave a "probable" diagnosis in 71% of parkinsonian patients at follow-up but in only 15% at the initial assessment.

DISCUSSION: The clinical diagnosis of the cause of parkinsonism at presentation was often incorrect, even when made by those with a special interest. In particular, Parkinson's disease was overdiagnosed. Research criteria were often unhelpful in clarifying the diagnosis, even after a median of 29 months of follow-up. Further research is required to identify factors that may be used to improve the accuracy of diagnosis at initial assessment.

Generally I agree that a diagnosis isn't important. With LBD, however, because some meds can really help (AChEIs) and some meds can really hurt some people (neuroleptics, narcotics), I think getting a diagnosis is important. Sadly, many don't get a diagnosis until something bad happens.

Mon Nov 17, 2008 12:25 pm

dorthea

Joined: Sat Oct 06, 2007 4:28 pmPosts: 781Location: LA

It seemed futile at first

...and sometimes, no matter how much you present to doctors, it seems impossible to get a diagnoses! Such has been my situation and the reason for my first post when I identified myself as The Impostor. But never mind, I was still fortunate enough to get a geriatric/psychiatrist to treat the symptoms with the variety of medicines recommended in the Dr Boeve Continuum and no longer did I have to "try" medicines for "regular" people. This regimen still needs to be tailored especially for my individual loved one, but we work within the realm of Lewy Body dementia. So whether he is a victim of LBD or not, now is not the time for me to know, it is enough for me to have guidelines to follow. I continually thank everyone on this panel for allowing an impostor to come in and you give me strength and understanding to have my husband here at home with me. I now see occasional smiles and yesterday as I was singing, "Let me call you Sweetheart... " I reached the part where it said, "with your eyes so blue", when he chimed in, "My eyes are not blue, they are brown". Whatever is the problem, he could not have known what color his eyes are without the Exelon Patch and the Namenda. I thank my doctors and I thank Dr Boeve.

_________________"See this lady she's 85 but she's nice", This is the way my husband, Mr B., introduced me in 2006 to the people only he knew. Death due to pneumonia. Lewy Body Dementia diagnosed post mortem at Mayo Clinic in Jacksonville Florida.

Mon Nov 17, 2008 6:42 pm

Irene Selak

Dorthea,
It's is the small things such as the color of his eyes that you will keep in your memory bank, I agree sometimes it really doesn't matter what the name of the disease is. I am glad the exelon patch is helping for now! We can only take each day as it comes!

This November '08 article may be of interest because over one-third of the patients diagnosed in this study had their diagnoses changed from PD to DLB later on. When the change was from PD to DLB or essential tremor, diagnostic "changes were most commonly a result of development of additional features, particularly early cognitive impairment and neuropsychiatric features, the results of radiological imaging, poor response to levodopa and lack of disease progression."

My November post below provided the text of a Reuters Health article written about this UK research. The research paper itself is available online at: (currently, it's free)
http://jnnp.bmj.com/cgi/reprint/79/11/1202

The tables, in particular, are worthwhile. I'd suggest scanning the tables for the disorders that interest you.

This paragraph from the Discussion section is worth noting: "Changing [diagnoses] between different parkinsonian syndromes may not alter management so dramatically as a trial of dopamine replacement therapy is often warranted but it will alter what information is given to the patient about prognosis. In addition, some clinicians may wish to avoid early levodopa in those with PD because of the risk of motor complications, while treatment withdrawal should always be considered where the syndrome is thought to be unresponsive. Similarly, while many experts would regard PD and DLB as being part of the same disease spectrum, we regarded them separately because their prognosis differs and dopamine agonists may be less suitable in DLB because of their greater neuropsychiatric toxicity."

I learned a few things from reading the full article. First, there is a Mini-Mental Parkinson (MMP) test available; it's a PD specific cognitive screening tool. "The MMSE and MMP may...be of some use in identifying parkinsonian patients who will go on to develop early dementia, although a larger study is needed to test this hypothesis." Second, PD is over-diagnosed. Third, "there have been reports of pathologically established cases of PD without an appreciable response to levodopa, making clinical diagnosis in life extremely difficult."

Here are extensive excerpts:

"Accurate diagnosis of PD is important both in clinical practice, where it will influence management, and in research, where the validity of findings may be compromised if studies include heterogenous conditions. This importance is likely to grow as neuroprotective strategies are developed that target specific pathological processes."

"Antemortem diagnosis currently relies on clinical assessment but, in most post-mortem series, the positive predictive value (PPV) of the final clinical diagnosis of PD has only been found to be between 76% and 90%. This can be improved with application of strict diagnostic criteria. For example, retrospective application of the UK Brain Bank diagnostic criteria improved the PPV in one study from 76% to 93%. However, application of these criteria meant that 32% of those with pathologically proven PD were not diagnosed clinically. Thus strict research based criteria increase specificity at the cost of reducing sensitivity."

"Much of the difficulty in the diagnosis of PD is in differentiating it from other disorders that cause parkinsonism. These include other neurodegenerative disorders such as dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy and corticobasal degeneration, and non-degenerative causes such as vascular parkinsonism or drug induced parkinsonism (eg, as a result of antidopaminergic drugs). Difficulty in initial diagnosis is further compounded by the existence of non-parkinsonian disorders that can mimic parkinsonism. Particular problems are presented by tremor disorders, most notably essential tremor, and primary gait disorders, especially higher level disorders such as those associated with cerebrovascular disease. The increasing prevalence of multiple comorbidities with age can further complicate matters. Indeed, general slowing in the elderly can be confused with bradykinesia, with subtle extrapyramidal signs being reported in up to 35% of subjects older than 65 years."

"Although diagnosing the cause of parkinsonism is problematic, few studies have systematically assessed changes in the clinical diagnosis over time. One study found that in a cohort of patients with early presumed PD, 8% had their diagnosis changed after a mean follow-up of 6 years because of either a poor levodopa response, the development of atypical clinical features, atypical imaging findings or post mortem."

"As part of the PINE pilot study, all patients from the lists of 18 general practices in Aberdeen (a population of approximately 148,000) presenting with a newly diagnosed possible or definite parkinsonian syndrome (excluding definite drug induced parkinsonism) were recruited by multiple overlapping strategies over an 18 month period. All were seen by a consultant neurologist with a special interest in PD or a supervised trainee, and underwent a standardised baseline assessment, including the Unified Parkinsonâs Disease Rating Scale (UPDRS) with video recording of the motor section, and assessment of atypical features, such as dysautonomia, gaze palsy and cognitive or psychiatric symptoms. In those who consented to detailed follow-up, cognitive testing was carried out using the Mini-Mental State Examination (MMSE) and the Mini-Mental Parkinson (MMP), a PD specific cognitive screening tool. Consenting patients had repeat yearly assessments with planned lifelong follow-up..."

"Patients were asked to consent to undergo structural neuroimaging with either CT or MRI and functional imaging of dopamine transporter uptake with N-v-fluoropropyl-2bcarbomethoxy-3b-(4-iodophenyl)-tropane (FP-CIT) single photon emission computed tomography (SPECT). FP-CIT SPECT scans were visually graded by a blinded consultant neuroradiologist as normal, abnormal or atypical (ie, abnormal but not in keeping with the pattern usually seen in neurodegenerative disease). CT and MRI images were assessed visually for burden of cerebrovascular disease and, in the case of MRI, midbrain atrophy and basal ganglia signal change but no formal criteria were applied."

"At baseline and at each yearly follow-up, the assessing (unblinded) clinician recorded up to three most likely clinical diagnoses without applying research criteria and gave a percentage certainty for each (eg, 90% certain PD). ... All available information was used to inform these diagnoses, including the results of any structural or functional imaging tests that were available at each assessment. Baseline diagnoses were reached after initial clinical assessment, before formal cognitive testing had been carried out."

"On each patientâs death, a final assessment was carried out, with review of general practitioner, hospital and research records, imaging tests and taking into account the results of post-mortem examinations where available. A final clinical or pathological diagnosis was then recorded."

"In this study, 4 years after the beginning of the incident period, the initial and latest clinical diagnoses (the one with the highest percentage certainty) were compared for all incident patients who had at least 1 year of follow-up data and the reason for any change identified from the notes. In those patients who died, the final clinical diagnosis was taken from the yearly assessment immediately prior to death. Formal research criteria were then applied retrospectively using patientsâ research records at baseline and latest yearly followup. For 37 of the patients, these criteria were applied independently by two assessors and the diagnoses reached were compared to assess inter-rater reliability. Differences in diagnosis were resolved by discussion. The criteria applied were as follows: the UK Brain Bank criteria for PD, the consensus criteria for DLB, the consensus criteria for multiple system atrophy, the Litvan criteria for progressive supranuclear palsy, Leesâ proposed criteria for vascular parkinsonism and the Lang criteria for corticobasal degeneration disregarding cognitive decline as a criterion for exclusion. Where patients met more than one set of criteria, a single best fit diagnosis was decided upon by consensus of two authors based on the information available."

"Of 82 incident patients identified, five were excluded from this study because they did not consent to follow-up and 11 were excluded because they died before their first yearly follow-up. The 66 remaining patients had a mean age of 75.0 years at diagnosis and were predominantly male (62%). At the initial assessment, symptoms had been present for a median of 12.5 months. Twenty-four patients died after at least 1 year of follow-up but no other patients were lost to follow-up. Only five patients had undergone examination of the brain at post mortem."

"Change in clinical diagnosis
Forty-six patients (70%) were initially diagnosed with idiopathic PD, with the most common alternate diagnoses being vascular parkinsonism, multiple system atrophy (all parkinsonian variant) and essential tremor (diagnosed in three patients; table 1). After a median follow-up of 29 months, the number diagnosed clinically with PD had fallen to 37 (56%), the most common alternative diagnoses being vascular parkinsonism and DLB."

"The clinical diagnosis changed between the baseline assessment and the latest follow-up in 22 patients (33%) and remained unchanged in 44 (table 2). There was no significant difference between these two groups in presenting symptoms, severity of their parkinsonian impairment (UPDRS) or duration of their symptoms at baseline (table 3). There was a nonsignificant trend towards greater cognitive impairment (MMSE and MMP) and older age in the group whose diagnoses changed. Most (18, 82%) changes occurred in the first year, three (6% of those with at least 2 years of follow-up) occurred within the second and one (3% of those with at least 3 years of follow-up) within the third."

"In those initially diagnosed with PD, the diagnosis was most likely to change to DLB (5/13, 38%) or essential tremor (3/13, 23%) (table 4). Changes were most commonly a result of development of additional features (n=7), particularly early cognitive impairment and neuropsychiatric features (n=5), the results of radiological imaging (n=6), poor response to levodopa (n=4) and lack of disease progression (n=6)."

"Changes in diagnosis in those initially diagnosed with conditions other than PD are shown in table 4. Changes were to PD (4/9, 44%), vascular parkinsonism (3/9, 33%) or DLB (2/9, 22%). The predominant reason for change to a diagnosis of PD was response to levodopa."

"Differences between latest clinical diagnosis and research diagnosis
Agreement between the two observers on the research criteria diagnosis was good (k=0.73), and agreement between research diagnosis and clinical diagnosis was very good (k=0.82). Details of the eight participants whose clinical and research diagnoses differed are shown in table 5."

"In the five patients who underwent post-mortem examination, the final clinical, research and pathological diagnoses agreed in two (one PD and one vascular) and in one the clinical diagnosis and pathological diagnosis agreed (PD with coexistent Alzheimerâs disease) while research criteria suggested possible DLB. The two participants whose clinical and antemortem research diagnoses were PD but whose post-mortem examinations showed PSP are described in table 5."

"DISCUSSION
In this study, one-third of the initial diagnoses of the cause of parkinsonism changed over a median of 29 months of followup. The majority of this change was a result of initial overdiagnosis of PD. The proportion of patients diagnosed with PD fell by 14% and most (59%) diagnostic changes were away from PD. These results are similar to previous studies, which showed that the clinical diagnosis of parkinsonism changed over time in 36% of patients attending a highly specialist clinic, and 16% of an incident cohort of patients with PD according to UK Brain Bank criteria had their initial diagnosis changed after about 3.5 years of follow-up."

"Over one-third (38%) of those misdiagnosed with PD had their diagnosis changed to DLB. This was usually because the symptomatic cognitive features of the disease were absent initially as, even using the strictest interpretation of the diagnostic criteria, parkinsonism can predate the onset of dementia by up to 1 year. However, the suggestion of a difference in cognitive scores between the change and no change groups would suggest that there may have been detectable deficits despite the lack of cognitive symptoms. The MMSE and MMP may, therefore, be of some use in identifying parkinsonian patients who will go on to develop early dementia, although a larger study is needed to test this hypothesis."

"Changes in diagnosis were usually as a result of level of response to treatment with levodopa or a dopamine agonist, lack of progression and development or resolution of atypical clinical features. This serves to highlight the need for regular follow-up and diagnostic revision in parkinsonian patients, and the diagnostic value of a trial of therapy. However, the results of therapeutic trials must be interpreted with caution, as PD may not show the classical excellent response to treatment, and there have been reports of pathologically established cases of PD without an appreciable response to levodopa, making clinical diagnosis in life extremely difficult. The role of functional imaging in the changes to diagnosis that took place is unclear. The results of FP-CIT SPECT scans supported change from initial clinical diagnoses in six patients, although in all but one of these cases (patient No 14, table 4), the clinical features were present that may have led to the change independently." [Robin's note: The diagnosis for patient #14 was changed from DLB to vascular parkinsonism.]

"The latest clinical diagnosis differed from the diagnosis on research criteria in eight patients (12%; table 5) usually because of exclusion criteria within the research criteria (patient Nos 23 and 24), or arbitrary time limits within the criteria (patient Nos 28 and 29)." [Robin's note: The diagnosis for patient #23 was changed from PD with concurrent AD to DLB, and for patient #24 from PD to MSA.]

"In two cases (patient Nos 25 and 30) there were features to support both diagnoses and it could be argued that either could be applied." [Robin's note: The diagnosis for patient #25 was changed from PD to MSA, and for patient #30 from DLB to vascular parkinsonism.]

"...there are also some limitations of this study that are worth noting. Firstly, our cohort was relatively small as it was drawn from a pilot study. A larger incidence study is currently underway and will allow analysis of similar data in a larger population. Secondly, while the revised diagnoses here are taken to be correct, it is likely that they will continue to change over time. Follow-up of this cohort will continue and so it will be possible to report the pattern of changes with longer followup in the future. Thirdly, the diagnoses were all supervised by a single consultant with an interest in PD and so our results may not be generalisable, particularly to more generalist clinics where the misdiagnosis rate may be higher. Finally and importantly, few diagnoses have been confirmed by post mortem and, therefore, it is not clear whether either the clinical or antemortem research diagnoses are correct. This is a problem with all clinical studies of parkinsonism but, because we have systematically tried to approach our participants for antemortem consent, we hope to obtain pathological confirmation in more of our participants over time. Studies of diagnostic accuracy that used brain bank material had the advantage of complete pathological confirmation but were disadvantaged by limited clinical information on which to base research diagnostic criteria and limited generalisability because post mortems are often performed on unusual or difficult cases."

"The clinical significance of misdiagnoses in parkinsonism varies. A change in diagnosis between a parkinsonian condition and a non-parkinsonian one (such as essential tremor) will have a significant impact on patient care as the treatments are quite different. Changing between different parkinsonian syndromes may not alter management so dramatically as a trial of dopamine replacement therapy is often warranted but it will alter what information is given to the patient about prognosis. In addition, some clinicians may wish to avoid early levodopa in those with PD because of the risk of motor complications, while treatment withdrawal should always be considered where the syndrome is thought to be unresponsive. Similarly, while many experts would regard PD and DLB as being part of the same disease spectrum, we regarded them separately because their prognosis differs and dopamine agonists may be less suitable in DLB because of their greater neuropsychiatric toxicity."

"In summary, we have demonstrated that even in those with a special interest, the accurate diagnosis of the cause of parkinsonism at presentation was difficult, that PD was overdiagnosed at first assessment and that research criteria were often unhelpful in clarifying the diagnosis, even after a median of 29 months of follow-up. Further research, in larger groups and over longer periods, is necessary to identify factors that may be used to improve the accuracy of diagnosis at the initial assessment. Our findings support the recent NICE guidelines that regular clinical review of those suffering from parkinsonism with careful attention to the diagnosis is essential in order that they receive appropriate care."

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